Biomarkers of Drug-Induced Kidney Toxicity

Ther Drug Monit. 2019 Apr;41(2):213-226. doi: 10.1097/FTD.0000000000000589.

Abstract

Blood urea nitrogen and serum creatinine are imperfect markers of kidney function because they are influenced by many renal and nonrenal factors independent of kidney function. A biomarker that is released directly into the blood or urine by the kidney in response to injury may be a better early marker of drug-induced kidney toxicity than blood urea nitrogen and serum creatinine. Urine albumin and urine protein, as well as urinary markers kidney injury molecule-1 (KIM-1), β2-microglobulin (B2M), cystatin C, clusterin, and trefoil factor-3 (TFF-3) have been accepted by the Food and Drug Administration and European Medicines Agency as highly sensitive and specific urinary biomarkers to monitor drug-induced kidney injury in preclinical studies and on a case-by-case basis in clinical trials. Other biomarkers of drug-induced kidney toxicity that have been detected in the urine of rodents or patients include IL-18, neutrophil gelatinase-associated lipocalin, netrin-1, liver-type fatty acid-binding protein (L-FABP), urinary exosomes, and TIMP2 (insulin-like growth factor-binding protein 7)/IGFBP7 (insulin-like growth factor-binding protein 7), also known as NephroCheck, the first Food and Drug Administration-approved biomarker testing platform to detect acute kidney injury in patients. In the future, a combined use of functional and damage markers may advance the field of biomarkers of drug-induced kidney toxicity. Earlier detection of drug-induced kidney toxicity with a kidney-specific biomarker may result in the avoidance of nephrotoxic agents in clinical studies and may allow for earlier intervention to repair damaged kidneys.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / metabolism
  • Albuminuria / chemically induced
  • Biomarkers / metabolism*
  • Biomarkers / urine*
  • Clusterin / urine
  • Cystatin C / urine
  • Drug-Related Side Effects and Adverse Reactions / prevention & control*
  • Exosomes / metabolism
  • Fatty Acid-Binding Proteins / urine
  • Hepatitis A Virus Cellular Receptor 1 / metabolism
  • Humans
  • Interleukin-18 / urine
  • Lipocalin-2 / urine
  • Netrin-1 / urine
  • Proteinuria / chemically induced
  • Tissue Inhibitor of Metalloproteinase-2 / urine
  • Trefoil Factor-3 / urine
  • beta 2-Microglobulin / urine

Substances

  • B2M protein, human
  • Biomarkers
  • Clusterin
  • Cystatin C
  • FABP1 protein, human
  • Fatty Acid-Binding Proteins
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • IL18 protein, human
  • Interleukin-18
  • Lipocalin-2
  • TIMP2 protein, human
  • Trefoil Factor-3
  • beta 2-Microglobulin
  • Tissue Inhibitor of Metalloproteinase-2
  • Netrin-1